1-(4-fluorophenyl)-2-(methylamino)ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-(4-fluorophenyl)-2-methylamino-ethanol (8.4 g) and triethylamine (7 mL) in tetrahydrofuran (80 mL) was added 3-chloro sulfonyl-thiophene-2-carboxylic acid methyl ester (10 g) on an ice bath over 20 minutes. The solution was brought back to room temperature and stirred for 1 hour. Ethyl acetate was added to the reaction solution, the resulting salt was removed by filtration, and solvent was evaporated at reduced pressure. The residue was purified by NH-silica gel column chromatography (hexane/ethyl acetate), and a pale yellow oily substance (15.6 g) was obtained. was brought back to room temperature the resulting salt was removed by filtration, and solvent was evaporated at reduced pressure The residue was purified by NH-silica gel column chromatography (hexane/ethyl acetate) a pale yellow oily substance (15.6 g) was obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: From 6-methyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-sulfonyl chloride (the compound of Preparation Example 13) (140 mg) and 1-(4-fluorophenyl)-2-methylamino ethanol (the compound of Preparation Example 17) (108 mg), the title compound (orange oily substance) (155 mg) was obtained as a mixture of diastereomers, in the same way as Preparation Example 41. the compound of Preparation Example 17) (108 mg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: From 1-(4-fluorophenyl)-2-methylamino-ethanol (the compound of Preparation Example 17) (186 mg) and 2-bromo-7-oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-3-sulfonyl chloride (the compound of Preparation Example 9) (330 mg), the title compound (373 mg) was obtained as a light brown candy-like substance, in the same way as Preparation Example 41. the compound of Preparation Example 9) (330 mg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: From 1-(4-fluorophenyl)-2-methylamino-ethanol (the compound of Preparation Example 17) (433 mg) and 7-oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-3-sulfonyl chloride (the compound of Preparation Example 7), the title compound (769 mg) was obtained as a colorless amorphous substance, in the same way as Preparation Example 41.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-(4-fluorophenyl)-2-methylamino ethanol (the compound of Preparation Example 17) (9.7 g) and t-butylbicarbonate (10.0 g) in a mixed solvent of tetrahydrofuran solution (100 mL) and an aqueous solution of saturated sodium bicarbonate (50 mL) was stirred at room temperature for 1.5 hours. The solution was diluted with ethyl acetate, and washed with water and saturated sodium chloride water. After drying the organic layer with anhydrous sodium sulfate, the residue that was obtained by evaporating the solvent at reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate), and the title compound (9.5 g) was obtained as a colorless solid. washed with water and saturated sodium chloride water After drying the organic layer with anhydrous sodium sulfate the residue that was obtained by evaporating the solvent at reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Benzyl-methyl-amino)-1-(4-fluorophenyl)-ethanol (54.6 g) and 10% palladium-carbon (5.8 g) was stirred in ethyl acetate-methanol (3:1) (800 mL) at 50° C. under hydrogen atmosphere for three hours. The catalyst was removed by filtration, and the filtrate was concentrated. After solidifying with an ether-hexane solvent, and the title compound (25.8 g) was obtained as a colorless solid. The catalyst was removed by filtration the filtrate was concentrated